SHBG's Prostate Cancer Ties

The potential role of the primary male androgen testosterone in prostate cancer is controversial. Many prostate tumors are known to be androgen responsive, and thus grow under the stimulation of male sex hormones. Whether or not these same hormones play a role in cancer initiation in the first place has been the subject of much research and debate. Studies suggesting that testosterone does not have a direct causative role in prostate cancer have been mounting in recent years. It has been shifting the benefits to risks assessment with testosterone medicines, and causing many clinicians to rethink their concerns about treating their aging male patients. A study published in a recent issue of the World Journal of Urology (World J Urol. 2011 Aug 11) is sure to add fuel to this debate.

The study reviewed data that was collected in Spain during a series of 1,000 prostate biopsies between September 2007 and January 2009. The researchers compared the cancer screening results with two important markers of testosterone activity, the serum hormone level (total testosterone) and the level SHBG (Sex Hormone Binding Globulin). SHBG is a binding protein that attaches to testosterone and prevents it from activating the cellular androgen receptor. It is often regarded as an inactivation protein for testosterone. Likewise, we usually regard the testosterone that is not bound to SHBG or other restrictive binding proteins as the free “active” component.

The results for the total testosterone level were in line with many other recent studies; no relationship was found between higher testosterone levels and prostate cancer. The only association with testosterone and prostate cancer was in hypogonadal (clinically low hormone levels) men. In this group, total testosterone levels were even lower in men with prostate cancer. With regard to SHBG, there was a strong association between higher levels and a positive cancer diagnosis. The exact nature of this relationship is unclear. It could mean many things, such as an active role of SHBG in disease, a preventative role of free testosterone; or even an effect rather than cause. More research is needed on this subject, though a much different picture than many expected has already been emerging.